The Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study (PROUDEST): A Multicenter Prospective Cohort Study Protocol (Preprint)

Background A growing body of evidence suggests that infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during pregnancy may affect maternal-fetal outcomes, with possible implications for the long-term development of exposed children. Objective The PRegnancy OUtcomes and child Development Effects of SARS-CoV-2 infection STudy (PROUDEST) is a multicenter prospective study designed to elucidate the repercussions of COVID-19 for mother-child global health. Methods The PROUDEST trial comprises two prospective sequential substudies. The PREGNANT substudy will assess the effects of SARS-CoV-2 infection on pregnancy, childbirth and puerperium clinically and from a mechanistic standpoint to elucidate the inflammatory and immunological phenomena underlying COVID-19 in relation to pregnancy. Pregnant women aged 18 to 40 years with laboratory-proven exposure to SARS-CoV-2 (group A, n = 300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B, n = 300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study assessing the offspring of women who entered the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment and metabolism from birth up to five years of age. It includes two comparison groups: group A (exposed, n = 300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls, n = 300) comprises children from nonexposed mothers. Results Recruitment began in July 2020, and as of September 2020, 115 pregnant women infected with SARS-CoV-2 during pregnancy and 80 newborns had been included. Data analysis is scheduled to start after all data have been collected. Conclusions Upon completion of the study, we expect to have obtained comprehensive data to provide a better understanding of the effects of SARS-CoV-2 and its inflammatory and immunological processes on pregnancy, puerperium and infancy. Our findings will inform clinical decisions regarding the care of exposed mothers and children and support the development of evidence-based public health policies. Clinicaltrial The PROUDEST study was registered on the Brazilian Register of Clinical Trials website (https://www. http://www.ensaiosclinicos.gov.br), ID RBR65QXS2, on June 13, 2020, where Brazilian clinical trials are exclusively registered. International registered report DERR1-10.2196/26477.